Stable long-term donor engraftment following reduced-intensity hematopoietic cell transplantation for sickle cell disease.
Reduced-intensity conditioning (RIC) regimens have the potential to decrease toxicities related to hematopoietic stem cell transplantation (HCT) in patients with sickle cell disease (SCD) and thus make HCT a more acceptable therapeutic option for this group of patients. We report the results of 7 patients enrolled on a study to evaluate safety and efficacy of HCT using bone marrow from an HLA matched sibling donor following an RIC regimen for patients with high-risk SCD. The conditioning regimen consisted of busulfan, fludarabine, equine antithymocyte globulin, and total lymphoid irradiation with shielding of the liver, lungs, heart, and gonads on day 1. Graft-versus-host disease (GVHD) prophylaxis consisted of cyclosporine and mycophenolate mofetil. The regimen was well tolerated, and all patients had hematopoietic recovery. Six of 7 patients are stably engrafted off immunosuppression and without sickle cell-related symptoms at 2 to 8.5 years after HCT. Consistent with the complete resolution of SCD related symptoms observed in the 6 engrafted patients, erythropoiesis of complete or predominantly donor origin was detected by red blood cell-specific chimerism assays, despite their having persistent mixed chimerism in the mononuclear and lymphoid compartments. These findings demonstrate the curative potential of allogeneic HCT after an RIC regimen in patients with SCD.
Krishnamurti
Lakshmanan
L
Children's Hospital of Pittsburgh, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania 15213, USA. krislx@chp.edu
Kharbanda
Sandhya
S
Biernacki
Melinda A
MA
Zhang
Wandi
W
Baker
K Scott
KS
Wagner
John E
JE
Wu
Catherine J
CJ
D000293:Adolescent; D000755:Anemia, Sickle Cell; D002648:Child; D016572:Cyclosporine / Q000008:administration & dosage; D005260:Female; D006085:Graft Survival / Q000187:drug effects; D006086:Graft vs Host Disease / Q000517:prevention & control; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage; D019520:Living Donors; D008297:Male; D009173:Mycophenolic Acid / Q000008:administration & dosage / Q000031:analogs & derivatives; D019653:Myeloablative Agonists / Q000008:administration & dosage; D035781:Siblings; D018183:Transplantation Chimera; D019172:Transplantation Conditioning; D014184:Transplantation, Homologous
D007166:Immunosuppressive Agents; D019653:Myeloablative Agonists; D016572:Cyclosporine; D009173:Mycophenolic Acid